Ovarian cancer, the leading cause of gynecologic cancer deaths, will be newly diagnosed in approximately 22,000 women in 2016 in the United States, with an estimated 14,000 deaths. This chapter will focus on the 95% of ovarian cancers that are of epithelial origin.
Risk factors for ovarian epithelial cancer include inheritance of ovarian cancer susceptibility genes, increasing age, infertility, nulliparity, endometriosis, polycystic ovary syndrome, use of an intrauterine device, and cigarette smoking.
The most common ovarian cancer susceptibility genes are BRCA1, BRCA2, and the mismatch repair (MMR) genes associated with hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch syndrome. Approximately 10% to 15% of women with ovarian cancer carry a mutation in one of these genes, and all women with epithelial ovarian cancer should be offered genetic testing for BRCA1 and BRCA2 mutations. In patients with a personal or family history of other HNPCC-related cancers (colorectal, small bowel or endometrial cancers or transitional cell cancers of the renal pelvis or ureter), HNPCC testing is recommended as well. There are different criteria for HNPCC genetic testing, including criteria and prediction models based on the number of affected relatives and age of onset, as well as tumor-based strategies often used in colorectal and endometrial cancers involving testing for microsatellite instability (MSI) or immunohistochemistry staining for mismatch repair proteins. The cumulative lifetime risk of ovarian cancer is 1.4% in patients without a susceptibility gene, 45% in BRCA1 carriers, 12% in BRCA2 carriers, and 3% to 13.5% in MMR gene mutation carriers.
Ovarian cancer screening with transvaginal ultrasonography or serum CA-125 testing is not effective and is not recommended for patients of average, or even high, risk.
For women with BRCA1, BRCA2, or MMR gene mutations, prophylactic bilateral salpingo-oophorectomy (BSO) is recommended after completion of childbearing. Prophylactic BSO is recommended by age 35 to 40 years for BRCA1 carriers and by age 45 years for BRCA2 carriers. For BRCA1 or BRCA2 carriers, prophylactic BSO decreases the risk of ovarian, fallopian tube, and primary peritoneal cancers by greater than 80% and decreases all-cause mortality to age 70 years by 77%. Recommendations for genetic testing for breast and ovarian cancer syndromes are discussed in Breast Cancer. In women with Lynch syndrome, BSO and hysterectomy are recommended because of the increased risk of endometrial cancer.
Oral contraceptives reduce the risk of ovarian cancer by 40% to 50%, with the greatest benefit seen after 15 years of use.
Ovarian cancer usually presents with advanced disease, either acutely with such symptoms as pleural effusions or bowel obstruction or subacutely with such symptoms as bloating, abdominal or pelvic pain, urinary frequency, or early satiety. An incidental ovarian mass may be found on routine examination. Initial studies for suspected ovarian cancer should include a pelvic examination, general physical examination, serum CA-125 level, complete blood count, liver chemistry tests, and transvaginal and transabdominal ultrasonography. Additional imaging with abdominal and pelvic CT or MRI and chest imaging with CT or chest radiography are added as clinically indicated. Patients with a high suspicion of ovarian cancer should be referred to a gynecologic oncologist.
For early ovarian cancer, surgical exploration is recommended for diagnosis because removing the ovarian cancer intact without rupture improves survival. For advanced ovarian cancers with peritoneal masses, ascites, or pleural effusions, fluid cytology or imaging-guided biopsy can be done, particularly in cases where the disease is not initially resectable and neoadjuvant chemotherapy may be used.
Staging and prognosis are shown in Table 43. Early stage, low grade, serous histology, extent of disease after surgical debulking, and young age are associated with improved survival. A recent analysis showed that 31% of patients diagnosed with ovarian cancer survived 10 years, with one third of these long-term survivors having stage III or IV cancer.
Surgical staging includes total hysterectomy, BSO, peritoneal washings, omentectomy, and pelvic and para-aortic lymph node sampling. In advanced ovarian cancer, surgical debulking, including the resection of metastatic disease, improves prognosis. The volume of residual disease after surgery correlates inversely with survival. Neoadjuvant chemotherapy is usually recommended for patients with initially unresectable disease.
Patients with early-stage ovarian cancer who have favorable histology may be treated with surgical resection alone. All other patients should receive adjuvant chemotherapy. Patients with stage III disease have improved survival, albeit with increased toxicity, from intraperitoneal along with intravenous chemotherapy; nevertheless, intraperitoneal therapy remains underused. Platinum-taxane chemotherapy is generally used for all stages. According to recent guidelines by the American Society of Clinical Oncology (ASCO) and Society of Gynecologic Oncology (SGO), patients with stage IIIC or IV ovarian cancer who are at high perioperative risk or who have a low likelihood of optimal tumor debulking should receive neoadjuvant chemotherapy followed by reevaluation for cytoreductive surgery.
For patients who achieve a complete or partial clinical remission after chemotherapy, a recent study has shown that the use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1 or BRCA2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo.
Second-look laparotomy to determine if a patient is in a pathologic response has not been shown to be beneficial.
Posttreatment surveillance consists of physical and pelvic examinations every 3 to 6 months for 5 years, then annually. The need to monitor serum CA-125 at each visit if initially elevated is controversial, as such monitoring does not improve survival. Other laboratory tests and imaging tests are recommended only as indicated for symptoms or findings suggesting recurrence.
Despite optimal treatment, 80% to 85% of women with stage III or IV ovarian cancer will relapse. Patients who relapse 6 months or more after initial chemotherapy are considered to have platinum-sensitive disease, have a better prognosis, and are usually treated with platinum-containing combination chemotherapy. Adding the angiogenesis inhibitor bevacizumab improves disease-free survival but not overall survival, and increases the risk of serious gastrointestinal toxicities including perforation. For patients with platinum-resistant disease, various single agents can be used palliatively, as can bevacizumab alone or with chemotherapy. For BRCA1 or BRCA2 carriers with recurrent ovarian cancer, the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib can be given after progression on chemotherapy.